Hereditary early-onset Parkinson's disease caused by mutations in PINK1

Eriza Maria Valente, Patrick M. Abou-Sleiman, Viviana Caputo, Miratul M K Muqit, Kirsten Harvey, Suzana Gispert, Zeeshan Ali, Domenico Del Turco, Anna Rita Bentivoglio, Daniel G. Healy, Alberto Albanese, Robert Nussbaum, Rafael González-Maldonado, Thomas Deller, Sergio Salvi, Pietro Cortelli, William P. Gilks, David S. Latchman, Roberk J. Harvey, Bruno Dallapiccola & 2 others Georg Auburger, Nicholas W. Wood

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Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6. families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.

Original languageEnglish
Pages (from-to)1158-1160
Number of pages3
JournalScience
Volume304
Issue number5674
DOIs
Publication statusPublished - May 21 2004

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Parkinson Disease
Phosphotransferases
Mutation
Nonsense Codon
Dopaminergic Neurons
Substantia Nigra
Missense Mutation
Neurodegenerative Diseases
Mitochondria
Cell Culture Techniques
Chromosomes
Amino Acids

ASJC Scopus subject areas

  • General

Cite this

Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., ... Wood, N. W. (2004). Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science, 304(5674), 1158-1160. https://doi.org/10.1126/science.1096284

Hereditary early-onset Parkinson's disease caused by mutations in PINK1. / Valente, Eriza Maria; Abou-Sleiman, Patrick M.; Caputo, Viviana; Muqit, Miratul M K; Harvey, Kirsten; Gispert, Suzana; Ali, Zeeshan; Del Turco, Domenico; Bentivoglio, Anna Rita; Healy, Daniel G.; Albanese, Alberto; Nussbaum, Robert; González-Maldonado, Rafael; Deller, Thomas; Salvi, Sergio; Cortelli, Pietro; Gilks, William P.; Latchman, David S.; Harvey, Roberk J.; Dallapiccola, Bruno; Auburger, Georg; Wood, Nicholas W.

In: Science, Vol. 304, No. 5674, 21.05.2004, p. 1158-1160.

Research output: Contribution to journalArticle

Valente, EM, Abou-Sleiman, PM, Caputo, V, Muqit, MMK, Harvey, K, Gispert, S, Ali, Z, Del Turco, D, Bentivoglio, AR, Healy, DG, Albanese, A, Nussbaum, R, González-Maldonado, R, Deller, T, Salvi, S, Cortelli, P, Gilks, WP, Latchman, DS, Harvey, RJ, Dallapiccola, B, Auburger, G & Wood, NW 2004, 'Hereditary early-onset Parkinson's disease caused by mutations in PINK1', Science, vol. 304, no. 5674, pp. 1158-1160. https://doi.org/10.1126/science.1096284
Valente EM, Abou-Sleiman PM, Caputo V, Muqit MMK, Harvey K, Gispert S et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004 May 21;304(5674):1158-1160. https://doi.org/10.1126/science.1096284
Valente, Eriza Maria ; Abou-Sleiman, Patrick M. ; Caputo, Viviana ; Muqit, Miratul M K ; Harvey, Kirsten ; Gispert, Suzana ; Ali, Zeeshan ; Del Turco, Domenico ; Bentivoglio, Anna Rita ; Healy, Daniel G. ; Albanese, Alberto ; Nussbaum, Robert ; González-Maldonado, Rafael ; Deller, Thomas ; Salvi, Sergio ; Cortelli, Pietro ; Gilks, William P. ; Latchman, David S. ; Harvey, Roberk J. ; Dallapiccola, Bruno ; Auburger, Georg ; Wood, Nicholas W. / Hereditary early-onset Parkinson's disease caused by mutations in PINK1. In: Science. 2004 ; Vol. 304, No. 5674. pp. 1158-1160.
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AU - Harvey, Kirsten

AU - Gispert, Suzana

AU - Ali, Zeeshan

AU - Del Turco, Domenico

AU - Bentivoglio, Anna Rita

AU - Healy, Daniel G.

AU - Albanese, Alberto

AU - Nussbaum, Robert

AU - González-Maldonado, Rafael

AU - Deller, Thomas

AU - Salvi, Sergio

AU - Cortelli, Pietro

AU - Gilks, William P.

AU - Latchman, David S.

AU - Harvey, Roberk J.

AU - Dallapiccola, Bruno

AU - Auburger, Georg

AU - Wood, Nicholas W.

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N2 - Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6. families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.

AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6. families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.

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